Emergence of letermovir resistance in solid organ transplant recipients with ganciclovir resistant cytomegalovirus infection: A case series and review of the literature

Transpl Infect Dis. 2021 Jun;23(3):e13515. doi: 10.1111/tid.13515. Epub 2020 Dec 6.


Ganciclovir (GCV)-resistant cytomegalovirus (CMV) infection is a common problem among solid organ transplant (SOT) recipients without prior CMV immunity (CMV D+/R-). GCV-resistant CMV represents a particular challenge for CMV management. Letermovir is a recently licensed antiviral agent for primary CMV prophylaxis in allogenic hematopoietic stem cell transplant (HSCT) recipients. Given the favorable safety profile and its oral bioavailability letermovir may be considered a valuable off-label option for secondary prophylaxis of GCV-resistant CMV in SOT recipients. Here, we describe our experience with letermovir as secondary prophylaxis for GCV-resistant CMV in two renal transplant recipients and review the literature in regard of previously published cases. Letermovir resistance emerged after a few months of secondary prophylaxis in the two renal transplant recipients. In both cases, the previously described UL56 C325Y letermovir resistance mutation was detected. In vitro studies of letermovir suggest a relatively low genetic barrier to resistance. Therefore, caution is warranted when using letermovir as secondary prophylaxis for GCV-resistant CMV infection.

Keywords: human cytomegalovirus infection (CMV); letermovir resistance; secondary CMV prophylaxis; solid organ transplant.

MeSH terms

  • Acetates
  • Antiviral Agents / therapeutic use
  • Cytomegalovirus
  • Cytomegalovirus Infections* / drug therapy
  • Drug Resistance, Viral
  • Ganciclovir / therapeutic use
  • Humans
  • Organ Transplantation*
  • Quinazolines
  • Transplant Recipients


  • Acetates
  • Antiviral Agents
  • Quinazolines
  • letermovir
  • Ganciclovir